Klinische FragestellungPränataler Hydrozephalus, Differentialdiagnose
Zusammenfassung
Umfassendes differentialdiagnostisches panel für Pränataler Hydrozephalus mit 78 bzw. insgesamt 116 kuratierten Genen gemäß klinischer Verdachtsdiagnose
220,9 kb (Erweitertes Panel: inkl. additional genes)
- Chorionzotten (CVS)
- Fruchtwasser (nach AC)
- Nabelschnurblut (NB)
NGS +
[Sanger]
Genpanel
Ausgewählte Gene
Name | Exon-Länge (bp) | OMIM-G | Referenz-Seq. | Erbgang |
---|---|---|---|---|
AKT3 | 1440 | NM_005465.7 | AD | |
AP1S2 | 474 | NM_003916.5 | XLR | |
ARSB | 1602 | NM_000046.5 | AR | |
B3GALNT2 | 1503 | NM_152490.5 | AR | |
B3GLCT | 1497 | NM_194318.4 | AR | |
B4GAT1 | 1248 | NM_006876.3 | AR | |
BLTP1 | 15018 | NM_015312.4 | AR | |
BUB1B | 3153 | NM_001211.6 | AR | |
CC2D2A | 4863 | NM_001080522.2 | AR | |
CCDC88C | 6087 | NM_001080414.4 | AR | |
CCND2 | 870 | NM_001759.4 | AD | |
CENPF | 9403 | NM_016343.4 | AR | |
CEP83 | 2106 | NM_001042399.2 | AR | |
COL4A1 | 5010 | NM_001845.6 | AD | |
CRB2 | 3858 | NM_173689.7 | AR | |
CRPPA | 1356 | NM_001101426.4 | AR | |
DAG1 | 2688 | NM_004393.6 | AR | |
DENND5A | 3864 | NM_015213.4 | AR | |
DHCR24 | 1551 | NM_014762.4 | AR | |
EEF2 | 2577 | NM_001961.4 | AD | |
EML1 | 2448 | NM_004434.3 | AR | |
ERF | 1647 | NM_006494.4 | AD | |
FAM20C | 1755 | NM_020223.4 | AR | |
FANCB | 2580 | NM_001018113.3 | XLR | |
FGFR1 | 2469 | NM_023110.3 | AD | |
FGFR2 | 2466 | NM_000141.5 | AD | |
FGFR3 | 2421 | NM_000142.5 | AD | |
FKRP | 1488 | NM_024301.5 | AR | |
FKTN | 1386 | NM_001079802.2 | AR | |
FLVCR2 | 1581 | NM_017791.3 | AR | |
GFAP | 1299 | NM_002055.5 | AD | |
GLI3 | 4743 | NM_000168.6 | AD | |
GPSM2 | 2055 | NM_013296.5 | AR | |
GUSB | 1956 | NM_000181.4 | AR | |
HYLS1 | 900 | NM_145014.3 | AR | |
IDS | 1653 | NM_000202.8 | XLR | |
KIAA0586 | 5005 | NM_001244189.2 | AR | |
KIDINS220 | 5431 | NM_020738.4 | AD | |
L1CAM | 3774 | NM_000425.5 | XLR | |
LAMB1 | 5361 | NM_002291.3 | AR | |
LARGE1 | 2271 | NM_004737.7 | AR | |
MAN2B1 | 3036 | NM_000528.4 | AR | |
MPDZ | 6126 | NM_003829.5 | AR | |
MYMK | 671 | NM_001080483.3 | AR | |
NF1 | 8457 | NM_001042492.3 | AD | |
NSD1 | 8091 | NM_022455.5 | AD | |
OSTM1 | 1005 | NM_014028.4 | AR | |
PIK3CA | 3207 | NM_006218.4 | AD | |
PIK3R2 | 2187 | NM_005027.4 | AD | |
PLG | 2433 | NM_000301.5 | AR | |
POMGNT1 | 1983 | NM_017739.4 | AR | |
POMGNT2 | 1743 | NM_032806.6 | AR | |
POMK | 1053 | NM_032237.5 | AR | |
POMT1 | 2244 | NM_007171.4 | AR | |
POMT2 | 2253 | NM_013382.7 | AR | |
PPP2R5D | 1356 | NM_006245.4 | AD | |
PTCH1 | 4344 | NM_000264.5 | AD | |
PTEN | 1212 | NM_000314.8 | AD | |
RNF125 | 699 | NM_017831.4 | AD | |
RPS6KA3 | 2223 | NM_004586.3 | XL | |
RXYLT1 | 1355 | NM_014254.3 | AR | |
SKI | 2187 | NM_003036.4 | AD | |
SMARCC1 | 3318 | NM_003074.4 | AD | |
SNX10 | 606 | NM_001199835.1 | AR | |
STRADA | 1185 | NM_001003786.3 | AR | |
SUFU | 1455 | NM_016169.4 | AR | |
SUMF1 | 1125 | NM_182760.4 | AR | |
TBC1D32 | 4318 | NM_152730.6 | AR | |
TCF12 | 2121 | NM_207036.2 | AD | |
TCIRG1 | 2493 | NM_006019.4 | AR | |
TNFRSF11A | 1851 | NM_003839.4 | AR | |
TRIM71 | 2611 | NM_001039111.3 | AD | |
TWIST1 | 609 | NM_000474.4 | AD | |
USP9X | 7713 | NM_001039590.3 | XL | |
WASHC5 | 3480 | NM_014846.4 | AR | |
ZBTB20 | 2226 | NM_001164342.2 | AD | |
ZIC2 | 1599 | NM_007129.5 | AD | |
ZIC3 | 1404 | NM_003413.4 | XLR |
Infos zur Erkrankung
Auf pränatalen Hydrozephalus (HC) wird in der Regel durch die beobachtete Ventrikulomegalie (VM) im pränatalen Ultraschall geschlossen, die z.B. auf erhöhten intrakraniellen Druck zurückzuführen ist, in der Regel durch Obstruktion verursacht, schließlich zur progressiven Makrozephalie führt. Die Begriffe HC und VM werden häufig synonym verwendet. Die sonographischen Zeichen umfassen ein heterogenes Spektrum von Zuständen, das von pathologischen Prozessen mit schwerwiegenden Folgen für die neurologische Entwicklung bis hin zu normalen Veränderungen reicht. Zu den Ursachen für gestörte Liquor-Zirkulation und -Obstruktion gehören Aquädukt- und Monro-Foramen-Stenose, Neuralrohrdefekte, Dandy-Walker-Malformation sowie primäre Hirnfehlbildungen wie Holoprosenzephalie, kortikale Entwicklungs- und Corpus-Callosum-Anomalien. Neben Chromosomenstörungen (Trisomien 21, 18, 13; komplexen Aberrationen etc.) und Kopienzahl-Varianten werden die genetischen HC-Syndrome auch durch viele verschiedene Einzelgenmutationen verursacht. Störungen der neuronalen Adhäsion, des Vesikel-Transports und der Wnt-Signalwege sind in diesem Zusammenhang ebenso anzuführen wie Dystroglykanopathien, Ziliopathien, RASopathien, lysosomale Speicherkrankheiten, gestörte Wachstums- und Transkriptionsfaktor-Expression neben zahlreichen komplexen genetischen Syndromen. So umfasst z.B. das L1-Syndrom ein breites Spektrum, das von schwer bis leicht reicht und drei klinische Phänotypen einschließt: den X-chromosomalen Hydrocephalus mit Stenose des sylvischen Aquädukts, das MASA-Syndrom (Mentale Retardierung, Aphasie, Spastische Paraplegie, Adduzierte Daumen) einschließlich der X-chromosomal-bedingten komplizierten hereditären spastischen Paraplegie Typ 1 und schließlich die X-gebundene komplizierte Corpus-Callosum-Agenesie. Alle Phänotypen können bei den betroffenen Personen in ein und derselben Familie beobachtet werden, was die Variabilität des Syndroms widerspiegelt. Neben Umwelt-bedingten Formen (Infektionen) und multifaktoriellen Geschehen werden beim monogenen HC alle klassischen Vererbungsmuster beobachtet. Trotz besonders umfangreicher Genpanels ist die DNA-diagnostische Ausbeute begrenzt, aber abhängig von der klinischen Aufarbeitung des Falls bzw. der betroffenen Familie. So schließt ein negatives molekulargenetisches Ergebnis die klinische Diagnose keineswegs aus.
Referenzen: https://www.ncbi.nlm.nih.gov/books/NBK1484/
https://www.annualreviews.org/doi/pdf/10.1146/annurev-neuro-070815-014023
- Allelic: Chondrodysplasia punctata, XLD (EBP)
- Allelic: Osteolysis, familial expansile (TNFRSF11A)
- Allelic: Paget disease of bone 2, early-onset (TNFRSF11A)
- Acrocallosal syndrome (KIF7)
- Al-Gazali-Bakalinova syndrome (KIF7)
- Alexander disease (GFAP)
- Alkuraya-Kucinskas syndrome (KIAA1109)
- Angiopathy, hereditary, with nephropathy, aneurysms + muscle cramps (COL4A1)
- Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
- Apert syndrome (FGFR2)
- Band heterotopia (EML1)
- Bardet-Biedl syndrome 13 (MKS1)
- Basal cell nevus syndrome (PTCH2)
- Brain small vessel disease with/-out ocular anomalies (COL4A1)
- CLAPO syndrome, somatic (PIK3CA)
- CLOVE syndrome, somatic (PIK3CA)
- COACH syndrome (CC2D2A)
- COACH syndrome 1 (TMEM67)
- COACH syndrome 3 (RPGRIP1L)
- CRASH syndrome (L1CAM)
- Carey-Fineman-Ziter syndrome (MYMK)
- Caudal regression syndrome (VANGL1)
- Cerebellar ataxia, impaired intellectual development, dysquilibrium syndrome 2 (WDR81)
- Chitayat syndrome (ERF)
- Chondrodysplasia + platyspondyly, distinctive brachydactyly, hydrocephaly, microphthalmia (HDAC6)
- Chudley-McCullough syndrome (GPSM2)
- Ciliary dyskinesia, primary, 1, with or without situs inversus (DNAI1)
- Coffin-Lowry syndrome (RPS6KA3)
- Coffin-Siris syndrome 3 (SMARCB1)
- Cole-Carpenter syndrome 1 (P4HB)
- Cole-Carpenter syndrome 2 (SEC24D)
- Congenital hydrocephalus, aqueductal stenosis, septal agenesis [panelapp] (SMARCC1)
- Corpus callosum abnormalities [panelapp] (SMARCC1)
- Craniosynostosis 1 (TWIST1)
- Craniosynostosis 3 (TCF12)
- Craniosynostosis 4 (ERF)
- Craniosynostosis, nonspecific (FGFR2)
- Crouzon syndrome (FGFR2)
- Desmosterolosis (DHCR24)
- Developmental + epileptic encephalopathy 1
- Dysplasminogenemia (PLG)
- Ellis-van Creveld syndrome (EVC2)
- Endocrine-cerebroosteodysplasia (CILK1)
- Epileptic encephalopathy, early infantile, 49 (DENND5A)
- Erythrocytosis, familial, 2 (VHL) 3
- Fanconi anemia, complementation group B (FANCB)
- Focal segmental glomerulosclerosis 9 (CRB2)
- Greig cephalopolysyndactyly syndrome (GLI3)
- Hartsfield syndrome (FGFR1)
- Heterotaxy, visceral, 1, XL (ZIC3)
- Holoprosencephaly 3 (SHH)
- Holoprosencephaly 5 (ZIC2)
- Holoprosencephaly 7 (PTCH1)
- Hydranencephaly with abnormal genitalia (ARX)
- Hydrocephalus due to aqueductal stenosis (L1CAM)
- Hydrocephalus with Hirschsprung disease (L1CAM)
- Hydrocephalus with cong. idiopathic intestinal pseudoobstruction (L1CAM)
- Hydrocephalus, cong., 1 (CCDC88C)
- Hydrocephalus, congenital communicating, 1 (TRIM71)
- Hydrocephalus, congenital, 2, with/-out brain or eye anomalies (MPDZ)
- Hydrocephalus, congenital, 3, with brain anomalies (WDR81)
- Hydrolethalus syndrome (HYLS1)
- Hydrolethalus syndrome 2 (KIF7)
- Intellectual developmental disorder, XL 29 (ARX)
- Jackson-Weiss syndrome (FGFR1, FGFR2)
- Joubert syndrome 12 (KIF7)
- Joubert syndrome 14 (TMEM237)
- Joubert syndrome 16 (TMEM138)
- Joubert syndrome 17 (CPLANE1)
- Joubert syndrome 2 (TMEM216)
- Joubert syndrome 20 (TMEM231)
- Joubert syndrome 23 (KIAA0586)
- Joubert syndrome 24 (TCTN2)
- Joubert syndrome 27 (B9D1)
- Joubert syndrome 28 (MKS1)
- Joubert syndrome 32 (SUFU)
- Joubert syndrome 34 (B9D2)
- Joubert syndrome 5 (CEP290)
- Joubert syndrome 6 (TMEM67)
- Joubert syndrome 7 (RPGRIP1L)
- Joubert syndrome 9 (CC2D2A)
- LADD syndrome (FGFR2, FGFR3)
- Lhermitte-Duclos syndrome (PTEN)
- Lissencephaly 5 (LAMB1)
- Lissencephaly, XL 2 (ARX)
- Lymphangioleiomyomatosis (TSC1)
- MASA syndrome (L1CAM)
- MEND: Male Ebp disorder with Neurologic Defects syndrome (EBP)
- Macrocephaly/autism syndrome (PTEN)
- Mannosidosis, alpha-, types I + II MAN2B1)
- Meckel syndrome 1 (MKS1)
- Meckel syndrome 11 (TMEM231)
- Meckel syndrome 2 (TMEM216)
- Meckel syndrome 3 (TMEM67)
- Meckel syndrome 5 (RPGRIP1L)
- Meckel syndrome 6 (CC2D2A)
- Meckel syndrome 7 (NPHP3)
- Meckel syndrome 8 (TCTN2)
- Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic (PIK3CA)
- Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (PIK3R2)
- Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (AKT3)
- Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (CCND2)
- Mental retardation, AD 35 (PPP2R5D)
- Mental retardation, XL 19 (RPS6KA3)
- Mental retardation, XL 99 (USP9X)
- Mental retardation, XL 99, syndromic, female-restricted (USP9X)
- Mental retardation, XL syndromic 5 (AP1S2)
- Microangiopathy + leukoencephalopathy, pontine, AD (COL4A1)
- Microphthalmia with coloboma 5 (SHH)
- Mosaic variegated aneuploidy syndrome 1 (BUB1B)
- Mucopolysaccharidosis II (IDS)
- Mucopolysaccharidosis VII (GUSB)
- Mucopolysaccharidosis type VI [Maroteaux-Lamy] (ARSB)
- Muenke syndrome (FGFR3)
- Multiple sulfatase deficiency (SUMF1)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anom.), A13 [MONDO:0014120] (B3GNT2)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 1 (POMT)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 10 (RXYLT1)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 11 (B3GALNT2)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 12 (POMK)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 13 (B4GAT1)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 2 (POMT2)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 3 (POMGNT1)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 4 (FKTN)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 5 (FKRP)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 6 (LARGE1)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 7 (CRPPA)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 8 (POMGNT2)
- Muscular dystrophy-dystroglycanopathy (cong. with brain + eye anomalies), type A, 9 (DAG1)
- Muscular dystrophy-dystroglycanopathy (cong. with mental retardation), type B, 1 (POMT)
- Muscular dystrophy-dystroglycanopathy (cong. with mental retardation), type B, 2 (POMT2)
- Muscular dystrophy-dystroglycanopathy (cong. with mental retardation), type B, 3 (POMGNT1)
- Muscular dystrophy-dystroglycanopathy (cong. with mental retardation), type B, 6 (LARGE1)
- Muscular dystrophy-dystroglycanopathy (cong. with/-out mental retardation), type B, 5 (FKRP)
- Muscular dystrophy-dystroglycanopathy (cong. without mental retardation), type B, 4 (FKTN)
- Muscular dystrophy-dystroglycanopathy (limb-girdle) type C, 8 (POMGNT2)
- Myotubular myopathy, XL ((MTM1)
- Nephronophthisis 11 (TMEM67)
- Nephronophthisis 18 (CEP83)
- Nephronophthisis 3 (NPHP3)
- Neural tube defects (VANGL2)
- Neural tube defects, susceptibility to (VANGL1)
- Neurofibromatosis, type 1 (NF1)
- Neurofibromatosis, type 2 (NF2)
- Orofaciodigital syndrome VI (CPLANE1)
- Orofaciodigital syndrome [MONDO:0015375] (TBC1D32)
- Osteopetrosis, AR (TCIRG1)
- Osteopetrosis, AR 5 (OSTM1)
- Osteopetrosis, AR 7 (TNFRSF11A)
- Osteopetrosis, AR 8 (SNX10)
- Otopalatodigital syndrome, type I + II (FLNA)
- Pallister-Hall syndrome (GLI3)
- Partington syndrome (ARX)
- Peters-plus syndrome (B3GLCT)
- Pfeiffer syndrome (FGFR1, FGFR2)
- Pheochromocytoma (VHL)
- Plasminogen deficiency, type I (PLG)
- Polyhydramnios, megalencephaly + symptomatic epilepsy (STRADA)
- Primrose syndrome (ZBTB20)
- Proliferative vasculopathy + hydranencephaly-hydrocephaly syndrome (FLVCR2)
- Proud syndrome (ARX)
- RHYNS syndrome (TMEM67)
- Raine syndrome (FAM20C)
- Renal-hepatic-pancreatic dysplasia 1 (NPHP3)
- Ritscher-Schinzel syndrome 1 (WASHC5)
- Robinow-Sorauf syndrome (TWIST1)
- SADDAN (FGFR3)
- Saethre-Chotzen syndrome (FGFR2)
- Saethre-Chotzen syndrome with/-out eyelid anomalies (TWIST1)
- Schizencephaly (SHH)
- Short-rib thoracic dysplasia 14 with polydactyly (KIAA0586)
- Shprintzen-Goldberg syndrome (SKI)
- Single median maxillary central incisor (SHH)
- Sotos syndrome 1 (NSD1)
- Spastic paraplegia, intellectual disability, nystagmus + obesity (KIDINS220)
- Spinocerebellar ataxia 26 (EEF2)
- Stromme syndrome (CENPF)
- Sweeney-Cox syndrome (TWIST1)
- Tenorio syndrome (RNF125)
- Tetra-amelia syndrome 1 (WNT3)
- Tuberous sclerosis-1 (TSC1)
- Tuberous sclerosis-2 (TSC2)
- VACTERL association (HOXD13)
- VACTERL association, XL (ZIC3)
- Ventriculomegaly and arthrogryposis (KIDINS220)
- Ventriculomegaly with cystic kidney disease (CRB2)
- Watson syndrome (NF1)
- Weyers acrofacial dysostosis (EVC2)
- von Hippel-Lindau syndrome (VHL)
- AD
- AR
- XL
- XLR
- Multiple OMIM-Ps
Bioinformatik und klinische Interpretation
Kein Text hinterlegt